The basic principle underlying this request for grant renewal is the assumption that the pathogenesis of alcoholic liver injury must be sought on a molecular level, and that the techniques of molecular biology should be applied to this problem. We will, therefore, address ourselves to problems involving several organelles of the liver cell. Mitochondria, which appear to be damaged by chronic ethanol consumption, will be studied in terms of the electron transport chain, oxidative phosphorylation, control points of the citric acid cycle, membrane biogenesis and morphologic changes by scanning electron microscopy. Exchange reactions involving phospholipid and protein transfer between organelles will be investigated. A new line of investigation will involve the plasma membrane, which is now realized to be important in the regulation of cell metabolism. Studies on the endoplasmic reticulum and Golgi complex will be continued. Changes in cell organelles will be correlated with studies of isolated liver cells and short term liver cell cultures. The effects of the metabolites of alcohol oxidation, acetaldehyde and acetate, will be assessed. Studies will be performed not only in the rat, but in our new models of alcoholic cirrhosis in the baboon, and transplantable hepatomas. These studies should yield insights into the basic molecular injury associated with alcohol abuse.